Extracellular nanovesicles-transmitted circular RNA has_circ_0000190 suppresses osteosarcoma progression

J Cell Mol Med. 2020 Feb;24(3):2202-2214. doi: 10.1111/jcmm.14877. Epub 2020 Jan 10.

Abstract

Under the microenvironment, tumour progression is substantially affected by cell-cell communication. In spite of the mediating effect of extracellular nanovesicles (EVs) on cell-cell communication by packaging into circRNAs, the effect of EVs circRNA hsa_circ_0000190 (circ-0000190) in osteosarcoma is still not clear. Circ-0000190 expressions in tissues and EVs from plasma were compared between osteosarcoma patients and controls. Thereafter, receiver operating characteristic (ROC) curve was drawn and area under the curve was calculated to examine whether the diagnostic results were accurate, and the effect of EVs circ-0000190 was dug out via the determination of cell phenotypes and animal assays. Results showed circ-0000190 exhibited an obvious reduction in EVs and tissues of osteosarcoma patients (P < .05). It was also discovered that EVs encapsulated the majority of circ-0000190, and EVs-encapsulated circ-0000190 could be applied to make a distinction between osteosarcoma patients and controls. Besides, EVs circ-0000190 in osteosarcoma cells transported from normal cells weakened the capacities of osteosarcoma cells to migrate, proliferate and invade, so as to block their biological malignant behaviours (P < .05). In addition, under the action of EVs circ-0000190, tumour growth was impeded and the expression of TET1 was inhibited via the competitive binding to miR-767-5p. In all, EVs circ-0000190 has a good prospect as it can be regarded as a new biomarker for detecting osteosarcoma. EVs circ-0000190 transported from normal cells to osteosarcoma cells impeded the in vitro and in vivo development of osteosarcoma, implying that EVs circ-0000190 exerts an effect on communication between normal cells and osteosarcoma cells in the carcinogenesis process of osteosarcoma.

Keywords: circ-0000190; biomarker; extracellular nanovesicles; miRNA; osteosarcoma.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • Mixed Function Oxygenases / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Circular / genetics*
  • ROC Curve
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Circular
  • Mixed Function Oxygenases